WO2006012885A1 - Systeme filtrant destine au traitement de liquides contenant des particules par separation sur membrane et par adsorption - Google Patents

Systeme filtrant destine au traitement de liquides contenant des particules par separation sur membrane et par adsorption Download PDF

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Publication number
WO2006012885A1
WO2006012885A1 PCT/DE2005/001372 DE2005001372W WO2006012885A1 WO 2006012885 A1 WO2006012885 A1 WO 2006012885A1 DE 2005001372 W DE2005001372 W DE 2005001372W WO 2006012885 A1 WO2006012885 A1 WO 2006012885A1
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WIPO (PCT)
Prior art keywords
filter system
particle
luminal
phase
plasma
Prior art date
Application number
PCT/DE2005/001372
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German (de)
English (en)
Inventor
Hans-Werner Heinrich
Original Assignee
Adexter Technology Limited
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
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Publication date
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Publication of WO2006012885A1 publication Critical patent/WO2006012885A1/fr

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M1/00—Suction or pumping devices for medical purposes; Devices for carrying-off, for treatment of, or for carrying-over, body-liquids; Drainage systems
    • A61M1/34—Filtering material out of the blood by passing it through a membrane, i.e. hemofiltration or diafiltration
    • A61M1/3472—Filtering material out of the blood by passing it through a membrane, i.e. hemofiltration or diafiltration with treatment of the filtrate
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M1/00—Suction or pumping devices for medical purposes; Devices for carrying-off, for treatment of, or for carrying-over, body-liquids; Drainage systems
    • A61M1/34—Filtering material out of the blood by passing it through a membrane, i.e. hemofiltration or diafiltration
    • A61M1/3472—Filtering material out of the blood by passing it through a membrane, i.e. hemofiltration or diafiltration with treatment of the filtrate
    • A61M1/3475—Filtering material out of the blood by passing it through a membrane, i.e. hemofiltration or diafiltration with treatment of the filtrate with filtrate treatment agent in the same enclosure as the membrane
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M1/00—Suction or pumping devices for medical purposes; Devices for carrying-off, for treatment of, or for carrying-over, body-liquids; Drainage systems
    • A61M1/34—Filtering material out of the blood by passing it through a membrane, i.e. hemofiltration or diafiltration
    • A61M1/3472—Filtering material out of the blood by passing it through a membrane, i.e. hemofiltration or diafiltration with treatment of the filtrate
    • A61M1/3486—Biological, chemical treatment, e.g. chemical precipitation; treatment by absorbents

Definitions

  • the invention relates to a filter system for the membrane-separated, adsorptive treatment of particle-containing liquids.
  • the field of application of the invention is medicine, in particular direct blood treatment.
  • Hemofiltration, hemodiafiltration, double filtration and plasma adsorption are milestones in the application of extra-corporeal therapeutic methods (or therapeutical apheresis). With plasma adsorption, it was possible for the first time to remove substances from the blood which are larger than albumin. Non-specific or specific factors are used for the binding of high-molecular substances in the flowing blood or plasma.
  • Electrostatic or hydrophobic interactions between the matrix and blood components routinely remove LDL, beta2-microglobulin, endotoxins, immunoglobulins, and circulating immune complexes from the blood.
  • the specific affinity of protein A for the Fc receptor of IgG allowed the development of immunoadsorbers used for the depletion of IgG for the treatment of eg severe forms of rheumatoid arthritis (Prosorba®).
  • Specific recognition sequences (antibodies, peptides) make it possible to remove clearly defined specificities from blood.
  • LDL Therasorb®, LDL Lipopak®
  • Lp (a) Lp (a) Lipopak®
  • acetylcholine receptor antibody MedisorbaMG®
  • Anti-ß1 adrenergic antibodies Corafin ®
  • inflammatory mediators EP 1163004
  • patient-specific, dissociated immune complex constituents as ligands for a patient-specific immunoadsorner (DE 19538641) is a special form on the path of increasingly targeted and personalized therapy.
  • blood is continuously withdrawn from a peripheral vein or a central venous catheter by means of a blood pump, usually with a blood flow of 60-120 ml / min in an extracorporeal circulation, and retransfused via another peripheral vein after removal of the pathogen.
  • a blood pump usually with a blood flow of 60-120 ml / min in an extracorporeal circulation, and retransfused via another peripheral vein after removal of the pathogen.
  • the provision of this intermittent extracorporeal blood circulation is subject to conditions similar to extracorporeal hemodialysis.
  • the filtrate flow in the primary separation is usually about 30% of the blood flow (plasma flow about 20-30 ml / min). Depending on the indication, usually one to two times the plasma volume of the patient is treated. In the treatment of one or two patient plasma volumes (assumption of a one-compartment model without re-distribution, synthesis or catabolism), theoretically a maximum can be achieved per treatment Reduction of the pathogen to 37% and 14% of the initial value can be achieved. However, these values are usually not realized in practice.
  • Non-selective plasmapheresis plasma exchange
  • the plasma in the extracorporeal circulation is separated from the blood cells by means of a membrane plasma separator or a centrifuge, the entire plasma is discarded and isovolemically substituted by an electrolyte solution plus human albumin or fresh plasma.
  • the substitution solution is combined with the separated blood cells and re-infused into the patient.
  • the advantage of the unselective plasma exchange lies in the simple structure of the extracorporeal circulation, the general applicability of the method for all apheresis zu ⁇ accessible pathogens, the effectiveness of not exactly known pathogen structure (eg in acetylcholine receptor negative myasthenia gravis) and the relatively low extracorporeal volume. Disadvantages are the immunoglobulin and coagulation factor depletion, the risk of incompatibility of the substituted foreign protein and a hyperoncotic substitution and the potential risk of infection in the transmission of pathogens with the substitution solution.
  • Membrane plasma separators consist of hollow fiber modules with synthetic membranes (eg polyethylene or polysulfone). The surface is between 0.2-0.5 m 2 , the pore size 0.2-0.5 microns. To monitor the extracorporeal circuit, specially developed devices are used for this purpose; Alternatively, the use of devices for hemoperfusion or hemofiltration is possible.
  • synthetic membranes eg polyethylene or polysulfone
  • the plasma separated by a plasma filter (primary separation) in a secondary circuit is purified either by a further filtration process (secondary separation) or by adsorption (immunological or physical). sikochemically) or by precipitation the pathogen is removed and the purified plasma is returned to the patient.
  • Double Filtration (Cascade Filtration, Membrane Differential Filtration)
  • This method uses after separation of the plasma in a secondary circuit, a second filter smaller pore size (cut-off 25-40 nm).
  • the aim is to recover albumin as quantitatively as possible, while retaining the higher molecular weight pathogenic protein in the secondary filter, which operates in the so-called "dead-end" mode (closure of the distal outlet of the distal outlet of the hollow fibers) spatial molecular conformation), it is only suitable for the removal of high-molecular pathogens such as IgM, LDL, fibrinogen or a-2-macroglobulin, therefore indications are eg hyperviscosity syndrome, M. Wadenström, cryoglobulinemia and hypercholesterolaemia Treatment of microcirculation disorders is referred to as Rheophere se.
  • immunoadsorption clinically the binding of immunologically active moieties to eg immobilized amino acids, peptides or proteins.
  • the methods based on adsorption either remove specific protein classes or specifically pathogenic antibodies.
  • LDL binding to anti-apoprotein B antibodies is also referred to as LDL immunoadsorption.
  • the Liposorber® system (Kaneka, Osaka, Hospal, Planegg) is based on the adsorption of LDL and Lp (a) from the plasma on dextran sulfate / cellulose (DSC).
  • the mechanism is based on an electrostatic interaction of the negatively charged sulfate groups of the dextran sulfate with the positively charged apo B of the two o.
  • G. Li popols. HDL, immunoglobulins and albumin are adsorbed only to a slight extent.
  • HELP® apheresis heparin-induced extracorporeal LDL precipitation, disposable product, Braun, Melsungen
  • LDL, Lp (a) and fibrinogen are precipitated from the plasma at an acidic pH of 5.12 by means of heparin in an extracorporeal circulation and filtered off.
  • Immunosorba® system (Fresenius HemoCare, St. Wendel) used as a ligand staphylococcal protein A with Sepharose as a carrier.
  • Prosorba® system (Fresenius HemoCare, St. Wendel) used as a ligand staphylococcal protein A with a silica matrix as a carrier
  • Globaffin® (Fresenius HemoCare, St. Wendel) immobilizes the synthetic peptide GAM® as a ligand on Sepharose CL-4B.
  • the binding properties correspond to those of protein A.
  • Coraffin® (Fresenius HemoCare, St. Wendel) specifically removes autoantibodies to the ß1-adrenergic receptor of the heart muscle. This is an indi ⁇ cation-specific process.
  • the Immusorba® system (ASAHI / Diamed, Cologne) uses non-reusable adsorbers based on tryptophan (TR-350L) or phenylalanine ligands (PH-350L), which are bound to a polyvinylethanol gel matrix. 3. cryofiltration
  • cryofiltration In cryofiltration (Asahi Medical, Tokyo, Diamed, Cologne), the separated plasma is cooled to 4 ° C. in a membrane differential filtration method to precipitate cryoglobulins and, after separation of the precipitates, with the aid of a cry - ofilters reinfused after reheating to body temperature.
  • adsorbing substances activated carbon, exchange resins
  • the size of the adsorber cartridge must ensure a sufficient exchange surface and contact time of the adsorbent.
  • the disposable adsorption cartridges consist of negatively charged polyacrylate ligands immobilized on polyacrylamide and electrostatically binding the atherogenic lipoproteins.
  • Filtration and adsorption processes can be combined in different ways.
  • Matson, et al. (US 6,287,516) describes a hemofiltration system consisting of a blood filter with downstream adsorber.
  • the ultrafiltrate from the filter (exclusion MW # 50,000 daltons) is pumped via a tubing system into an adsorber unit where the sepsis mediators are bound.
  • the ultrafiltrate thus treated can be combined with the primary filtered blood by another pump-tube valve system and reinfused into the patient.
  • the object of the invention is to provide a whole blood treatment unit which is characterized by a simple system structure. This is to blood flow (up to 160 ml / min) and shorter treatment times can be achieved
  • the object of the invention is to combine in this treatment unit, the advantages of membranes and particles and to achieve the elimination of pumps and additional hose connections.
  • a filter system for the simultaneous separation and adsorptive treatment of particle-containing liquids (Figure 1). It consists of a housing in which
  • Hollow fiber membranes are arranged so that the inlet and outlet openings for the liquids are outside the housing and the
  • the particle-containing liquid to be adsorbed be separated by filters having a pore size smaller than the particle diameter into a particle-free, extra-luminal and particle-containing intra-luminal phase. It is also essential that the housing simultaneously serves for receiving the adsorber material, the adsorber material consisting of particles having a diameter greater than the pore diameter of the membrane.
  • the object of the invention is achieved in that, in a self-contained housing made of biocompatible material, known plasma filters (membrane filters) are used. Hollow tubes) are arranged with the usual pore diameter of 0.2 to 0.5 microns.
  • the membrane material used may be cellulose derivatives or synthetic materials such as polysulfones or polyamides.
  • the housing serves as a receptacle for the functionalized particles. Polysulfone, polyacrylonitrile, polymethyl methacrylate, polyvinyl alcohol, polyamides, polycarbonates and cellulose derivatives can be used as material for the particles. Introduced into the flowing blood, the plasma passes the membrane according to the pressure gradient and the pore size.
  • the plasma now flows through the adsorber gel, consisting of unspecific or specifically functionalized micro-particles having a diameter above the pore diameter of the membrane.
  • the plasma which has been purified so specifically by certain bioactive substances, is combined in the housing with the intra-luminal plasma filter blood stream and reinfused into the patient as purified whole blood.
  • a system of filters prevents micro-particles from entering the bloodstream.
  • the filter system according to the invention is suitable for material separations of all kinds from liquid (extra-luminal) phases, where the particle-containing (intra-luminal) phase is to be further used in a closed system after reintroduction of the liquid phase treated according to the invention.
  • the experimentally used device for the removal of antigens from whole blood consists of a hollow-fiber plasma separator (A), the lower Gezzaus ⁇ part by an inserted cylinder (B), in which the Adsorbergel surrounds the hollow fibers has been replaced.
  • the blood plasma released by the transmembrane pressure must pass through the adsorber and is thereby freed of the target substances.
  • the plasma separation module consisted of a 0.4 m 2 hollow fiber filter (A).
  • the adsorber vessel contained 60 ml Sepharose, to which 5 mg IgY (vitellin antibodies from the eggs of chickens inoculated with IL6) were covalently bound per ml Sepharose.
  • the binding capacity of the adsorber was 72 ⁇ g IL6.
  • the blood flow rate was set to about 120 ml / min.
  • the module can be operated easily.
  • the treated amount of plasma was 1, 5 I.
  • the initial IL6 concentration of 500 pg / ml was lowered to 200 pg / ml during the 60 min adsorption period. This corresponds to a depletion of 60% in a single pass of the total plasma volume through the adsorber according to the device shown in Fig. 1.

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  • Health & Medical Sciences (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Biomedical Technology (AREA)
  • Engineering & Computer Science (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Hematology (AREA)
  • Anesthesiology (AREA)
  • Vascular Medicine (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Biodiversity & Conservation Biology (AREA)
  • Cell Biology (AREA)
  • Molecular Biology (AREA)
  • External Artificial Organs (AREA)

Abstract

L'invention concerne système de filtration et d'adsorption qui réunisse les propriétés de la filtration sur membrane et les propriétés de l'adsorption sur les particules dans un boîtier fermé.
PCT/DE2005/001372 2004-07-30 2005-07-29 Systeme filtrant destine au traitement de liquides contenant des particules par separation sur membrane et par adsorption WO2006012885A1 (fr)

Applications Claiming Priority (2)

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DE102004037475A DE102004037475A1 (de) 2004-07-30 2004-07-30 Filtersystem zur membrangetrennten, adsorptiven Behandlung partikelhaltiger Flüssigkeiten
DE102004037475.9 2004-07-30

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WO2006012885A1 true WO2006012885A1 (fr) 2006-02-09

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Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8585682B2 (en) 2008-02-09 2013-11-19 Renephra Limited Fluid extraction or filtration device, associated materials and methods
US9278969B2 (en) 2005-08-25 2016-03-08 Novartis Ag Organic compounds
EP3600485A4 (fr) * 2017-03-27 2021-01-06 Cytosorbents Corporation Procédés d'élimination de toxines du sang à l'aide d'un circuit extracorporel constitué d'un module de filtre à fibres creuses et d'un sorbant polymère associé
WO2022216510A1 (fr) * 2021-04-06 2022-10-13 Exthera Medical Corporation Milieu de filtration
US11844895B2 (en) 2014-04-24 2023-12-19 Exthera Medical Corporation Method for removing bacteria from blood using high flow rate
US11911551B2 (en) 2016-03-02 2024-02-27 Exthera Medical Corporation Method for treating drug intoxication

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE102016107483A1 (de) * 2016-04-22 2017-10-26 Poromembrane Gmbh Wasseraufbereitungsvorrichtung

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0139949A1 (fr) * 1983-08-19 1985-05-08 Kanegafuchi Kagaku Kogyo Kabushiki Kaisha Appareil pour l'épuration du sang
WO1993002777A1 (fr) * 1991-07-26 1993-02-18 Research Medical, Inc. Systeme de sorbants pour filtre de plasma servant a extraire des constituants du sang et systeme de transport de masse ameliore
WO1997014964A2 (fr) * 1995-10-05 1997-04-24 Privates Institut Bioserv Gmbh Immuno-adsorbants specifiques a chaque patient pour une apherese extracorporelle et procede de fabrication correspondant
US6497675B1 (en) * 2000-04-17 2002-12-24 Renal Tech International Llc Device for extracorporeal treatment of physiological fluids of organism

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0139949A1 (fr) * 1983-08-19 1985-05-08 Kanegafuchi Kagaku Kogyo Kabushiki Kaisha Appareil pour l'épuration du sang
WO1993002777A1 (fr) * 1991-07-26 1993-02-18 Research Medical, Inc. Systeme de sorbants pour filtre de plasma servant a extraire des constituants du sang et systeme de transport de masse ameliore
WO1997014964A2 (fr) * 1995-10-05 1997-04-24 Privates Institut Bioserv Gmbh Immuno-adsorbants specifiques a chaque patient pour une apherese extracorporelle et procede de fabrication correspondant
US6497675B1 (en) * 2000-04-17 2002-12-24 Renal Tech International Llc Device for extracorporeal treatment of physiological fluids of organism

Cited By (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US9278969B2 (en) 2005-08-25 2016-03-08 Novartis Ag Organic compounds
US8585682B2 (en) 2008-02-09 2013-11-19 Renephra Limited Fluid extraction or filtration device, associated materials and methods
US9808377B2 (en) 2008-02-09 2017-11-07 Renephra Limited Fluid extraction or filtration device, associated materials and methods
US11844895B2 (en) 2014-04-24 2023-12-19 Exthera Medical Corporation Method for removing bacteria from blood using high flow rate
US11911551B2 (en) 2016-03-02 2024-02-27 Exthera Medical Corporation Method for treating drug intoxication
EP3600485A4 (fr) * 2017-03-27 2021-01-06 Cytosorbents Corporation Procédés d'élimination de toxines du sang à l'aide d'un circuit extracorporel constitué d'un module de filtre à fibres creuses et d'un sorbant polymère associé
US11202855B2 (en) 2017-03-27 2021-12-21 Cytosorbents Corporation Methods for removal of toxins from blood using an extracorporeal circuit comprised of a hollow-fiber filter module and polymer sorbent in combination
WO2022216510A1 (fr) * 2021-04-06 2022-10-13 Exthera Medical Corporation Milieu de filtration

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